Assessment of metastatic traits of the cells with hybrid phenotype in breast cancer

Mukhamedzhanov RK1,4, Grigoryeva ES2, Tashireva LA2, Perelmuter VM2, Zavyalova MV1,2, Savelieva OE2,3
About authors

1 Siberian State Medical University, Tomsk, Russia

2 Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia

3 Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia

4 Regional Children’s Clinical Hospital, Vladimir, Russia

Correspondence should be addressed: Olga E. Savelieva
Litovskaya, 2, Saint-Petersburg, 194100; ur.liam@anihcehc_aglo

About paper

Funding: the study was supported by the RSF grant № 21-15-00140.

Author contribution: Mukhamedzhanov RK — literature analysis, data acquisition and statistical processing, manuscript writing; Grigoryeva ES — data acquisition and analysis, manuscript writing; Tashireva LA — study design, manuscript editing; Perelmuter VM — data interpretation, manuscript editing; Zavyalova MV — study planning, manuscript editing; Savelieva OE — study planning and management, data analysis and interpretation, manuscript writing.

Compliance with the ethical standards: the study was approved by the Ethics Committee of the Cancer Research Institute, Tomsk National Research Medical Center (protocol № 10 of 24 April 2015) and conducted in accordance with the Federal Laws of the Russian Federation (№ 152, 323, etc.), the Declaration of Helsinki (1964) and all subsequent amendments and supplements regulating the research involving human biomaterials. The informed consent to study participation was submitted by all subjects.

Received: 2023-07-04 Accepted: 2023-08-22 Published online: 2023-08-31

Nowadays, great attention is paid to the study of circulating tumor cells (CTCs) due to their key role in distant metastasis. At the same time there is little data on the properties of circulating cells showing simultaneous expression of the leukocyte and epithelial markers and their possible role in tumor progression and chemotherapy resistance. The study was aimed to assess subpopulations of cells with hybrid epithelial/leukocyte phenotype and estimate the features of stemness, epithelial–mesenchymal transition (EMT), and integrin interface, which determine the cells’ possible metastatic properties in breast cancer (BC). The survey data from 128 patients with invasive breast carcinoma of no special type were included. Multicolor flow cytometry was used to assess the population structure and metastatic potential of the cells circulating in blood and primary tumor cells with hybrid phenotype. The primary tumor cell suspension was prepared by mechanical disaggregation. The high degree of heterogeneity was noted in the population of cells with hybrid phenotype, including the combination of the stemness and EMT features, and diverse integrin interface. Cells with hybrid phenotype are involved in the mechanisms underlying lymph node and distant metastasis. In lymph node metastasis, metastatic potential of these cells is associated with the stemness features (р = 0.0422) and co-expression of β3-, β4-, and αVβ5-integrins (р = 0.0338). In distant metastasis, metastatic potential of hybrid cells is associated with the stemness features (р = 0.015) and is not associated with the EMT features and integrin expression.

Keywords: circulating tumor cells, integrins, metastasis, hybrid cells, stemness, epithelial-mesenchymal-transition